Amenorrhea is a common clinical problem affecting up to 3% of premenopausal women, 25-30% of whom are hyperprolactinemic. Women with hyperprolactinemia are often followed without therapy, despite a relative or absolute estrogen deficiency, often comparable to that seen in menopausal women. The deleterious systemic consequences of chronic estrogen deficiency, such as osteoporosis and premature vascular disease have been determined in menopausal women. The long-term effects and indications for therapy of functional hypogonadism in young amenorrheic women are as yet undefined and will be investigated in this application. The first goal of this proposal is to determine the risk of osteoporosis and indications for therapy in subsets of amenorrheic women. Our previous studies have demonstrated osteopenia in hyperprolactinemic women, and other workers have identified osteopenia in other amenorrheic groups. It is unknown whether the presence of osteopenia is an indication for therapy in these subjects. We will investigate whether untreated amenorrheic women have progressive osteopenia as documented by serial peripheral and trabecular bone density determinations. We will also investigate whether osteopenia can be arrested or improved in hyperprolactinemic women treated with bromocriptine or calcium supplementation. The relative importance of prolactin (PRL), estrogen, androgens, nutrition, and exercise will be investigated. The second goal is to determine the presence of abnormal serum cholesterol, triglycerides, and high density lipoprotein/low density lipoprotein ratios in amenorrheic women as risk factors for coronary artery disease. These studies are crucial to identify which patients may benefit from restoration of normal gonadal function. The third goal is to investigate the use of an LHRH analogue, D-Trp-6-Pro-9-NEt-LRF, as a novel potential therapy for patients with PRL-secreting tumors. Although acute LHRH administration causes a rise in both gonadotropins and PRL, chronic LHRH analogue use decreases gonadotropin, PRL and gonadal steroid secretion. In addition, chronic LHRH analogue administration has been shown to decrease the size of PRL-secreting tumors in experimental animals. Patients with PRL-secreting tumors who demonstrate a rise in PRL after an acute LHRH bolus will be studied to determine whether chronic LHRH administration can decrease PRL secretion. LHRH analogues may be a potentially useful therapy in a subset of patients with pituitary tumors who require additional treatment.